Dengue virus is a flavivirus of the Flaviviridae family. Dengue causes an estimated 390 million infections worldwide each year and hundreds of thousands of cases of severe dengue disease, known as Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome. Dengue virus causes more human death and disease than any other mosquito-borne viral infection, with the most severe disease burden among children under age 15; yet there is no licensed, effective vaccine to prevent this disease. The goal of this study is to move the global community closer to realizing a safe and effective vaccine against dengue through a Phase I/II clinical trial to evaluate the safety, tolerability and immunogenicity of a lie attenuated tetravalent dengue virus vaccine in Dhaka, Bangladesh. The investigational tetravalent vaccine was developed at NIAID by Steve Whitehead, PhD and tested through a decade of monovalent and multi-valent Phase I and II clinical trials in nearly 800 US-based flavivirus-nave and experienced adults at the University of Vermont's Vaccine Testing Center and the Johns Hopkins Center for Immunization Research. The specific vaccine formulation under investigation is well-tolerated and immunogenic in this population, and the next critical step for this vaccine is testing in endemic populations where people are naturally exposed to dengue. The specific aims of the dengue vaccine clinical trial are: 1) to determine the safety and tolerability of the tetravalent dengue vaccine candidate in previously dengue-exposed adults in Bangladesh; 2) to determine the immunogenicity of the dengue vaccine candidate in dengue-exposed Bangladeshi adults; and 3) to determine the extent to which vaccination could lead to immunopathogenesis upon exposure to wild-type dengue either pre- or post-vaccination. The study design is a randomized, double- masked and placebo-controlled trial. The target population is dengue-exposed adults living in the high population density urban setting of Dhaka, Bangladesh. Anticipated enrollment includes 120 dengue-experienced adults: 90 vaccines and 30 placebos.